Is SRC p.Pro307Ser (c.919C>T) pathogenic?

SRC p.Pro307Ser (c.919C>T) is classified Uncertain significance in SRC (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.8578); Very rare (popmax 6.84e-05%); Associated with thrombocytopenia 6.

What condition is associated with SRC p.Pro307Ser (c.919C>T)?

SRC p.Pro307Ser (c.919C>T) is associated with thrombocytopenia 6 (ClinVar).

How common is SRC p.Pro307Ser (c.919C>T) in the general population?

SRC p.Pro307Ser (c.919C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about SRC p.Pro307Ser (c.919C>T)?

AlphaMissense predicts likely pathogenic (score 0.8578) — an in-silico prediction, not a clinical call.

SRC p.Pro307Ser

Q: How is Hereditary thrombocytopenia with early-onset myelofibrosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.919C>T · rs2516461256 · VCV2584809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8578 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

thrombocytopenia 6

Computational evidence

Protein change
AlphaMissense	0.8578	likely pathogenic
REVEL	0.632	indeterminate
SaProt	LLR -11.91	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 5,565 bp · p 1.1e-23 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,612 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SRC
Protein: p.Pro307Ser
Coding: c.919C>T
MANE Select: NM_198291
dbSNP: rs2516461256
Type: single nucleotide variant
Location: chr20:37400174 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 307: the protein kinase domain; an α-helix

Full SRC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombocytopenia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary thrombocytopenia with early-onset myelofibrosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Neonatal

Similar variants

SRC p.Glu527Lys Pathogenic/Likely pathogenic ★★ same condition
SRC p.Gln529Glu Uncertain significance ★ ⚠ same condition
SRC p.Thr357Ile Uncertain significance ★ ⚠ same condition
SRC p.Glu492Lys Uncertain significance ★★ ⚠ same type
SRC c.1117-180C>T Benign ★★ same type
SRC c.1117-9C>T Likely benign ★★ same type
SRC c.1271-55= Benign ★★ same type
SRC c.449+9C>T Benign/Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/src-p-pro307ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown